T1D Clinical Trial Simulator

Simulate Type 1 Diabetes Prevention Clinical Trials

Individual Characteristics

Population:

Population from natural history studies

Virtual population (MVND method)

Virtual population (ctree method)

% of individuals with GADA AAb*:

Baseline HbA1c Interval (%)*:

% of individuals with IA2A AAb*:

Baseline GLU0 Interval (mg/dL)*:

Baseline GLURATIO Interval*:

Baseline Body Mass Index Interval (kg/m²):

Baseline Age Interval (Years):

Baseline GLU120 Interval (mg/dL):

Baseline PEP120 Interval (ng/dL):

Baseline PEP0 Interval (ng/dL):

% of individuals with a relative with T1D:

% of Males:

* Individual characteristics directly affecting the model parameters.

Available number of individuals (after the filter was applied) for clinical trial simulation

Population characteristics distribution - continuous

Population characteristics distribution - categorical

Clinical Trial Design

Number of Subjects in Placebo Arm:

Dropout Distribution for Placebo Arm:

Exponential Uniform

Dropout Rate for Placebo Arm:

Number of Subjects in Treatment Arm:

Dropout Distribution for Treatment Arm:

Exponential Uniform

Dropout Rate for Treatment Arm:

Duration of Subjects Follow-up (Years since Randomization):

Assessment Interval (Months):

Significance level for logRank test:

Assumed Drug Effect

Effect of the drug on the DP50 parameter (Increment x-times)

Number of Clinical Trial Replicates:

Type 1 Diabetes Prevention Clinical Trial Simulation Results

Download Report

Download

Stratification choice 1 (x-axis)

Parameter Selection

Range:

Number of datapoints:

Stratification choice 2

Parameter Selection

Range:

Number of datapoints:

Stratification choice 3

Parameter Selection

Range:

Number of datapoints:

Simulation details

Number of Clinical Trial replicates:

Type 1 Diabetes Prevention Clinical Trial Simulation Results (Power Curves)

MVND: Multivariate Normal Distribution (Reference: Tannenbaum, SJ, et al. Simulation of correlated continuous and categorical variables using a single multivariate distribution. Journal of Pharmacokinetics and Pharmacodynamics. 2006; 33(6):773-94.)
ctree: classification and regression trees method (Reference: Nowok, B, et al. synthpop: Bespoke Creation of Synthetic Data in R. Journal of Statistical Software. 2016; 74(11):1–26.)
DPmax: maximum GLU120 change
DP50: time producing 50% of DPmax
AAb: autoantibody
FDR: first degree relative of an individual with T1D
GADA: glutamic acid decarboxylase AAb
GLU0: fasting glucose measurement (0 min of OGTT)
GLU120: stimulated glucose measurement (120 min of OGTT)
HLA: human leukocyte antigen
IA2A: insulinoma associated protein-2 AAb
IAA: insulin AAb
OGTT: oral glucose tolerance test
PEP0: C peptide level at 0 min of OGTT
PEP120: C peptide level at 120 min of OGTT
T1D: type 1 diabetes
TEDDY: The Environmental Determinants of Diabetes in the Young
ZnT8: zinc transporter-8 AAb
BAGE: age at baseline
BSCORE_BMI: body mass index at baseline
BSCORE_GLU0: fasting glucose measurement(0 minutes of OGTT) at baseline
BSCORE_GLU120: stimulated glucose measurement(120 minutes of OGTT) at baseline
BSCORE_GLUDELTA: BSCORE_GLU120 - BSCORE_GLU0
BSCORE_GLURATIO: BSCORE_GLU120/BSCORE_GLU0
BSCORE_HbA1c: glycated hemoglobin result at baseline
BSCORE_PEP0: C peptide level at baseline (0 minutes of OGTT)
BSCORE_PEP120: C peptide level at baseline (120 minutes of OGTT)
BSCORE_PEPDELTA: BSCORE_PEP120 - BSCORE_PEP0
BSCORE_PEPRATIO: BSCORE_PEP120/BSCORE_PEP0
BSCORE_2AA: presence of at least 2 AAbs at baseline
BSCORE_3AA: presence of at least 3 AAbs at baseline
BSCORE_4AA: presence of at least 4 AAbs at baseline
BSCORE_GADA: GADA presence at baseline
BSCORE_GADA_IA2A: presence of GADA and IA2A at baseline
BSCORE_GADA_IA2A_IAA: presence of GADA, IA2A and IAA at baseline
BSCORE_GADA_IA2A_IAA_ZNT8: presence of GADA, IA2A, IAA and ZNT8 at baseline
BSCORE_GADA_IA2A_ZNT8: presence of GADA, IA2A and ZNT8 at baseline
BSCORE_GADA_IAA: presence of GADA and IAA at baseline
BSCORE_GADA_IAA_ZNT8: presence of GADA, IAA and ZNT8 at baseline
BSCORE_GADA_ZNT8: presence of GADA and ZNT8 at baseline
BSCORE_HLA_CATEGORY: HLA category as determined by TEDDY's increased risk groups
BSCORE_IA2A: IA2A presence at baseline
BSCORE_IA2A_IAA: presence of IA2A and IAA at baseline
BSCORE_IA2A_IAA_ZNT8: presence of IA2A, IAA and ZNT8 at baseline
BSCORE_IA2A_ZNT8: presence of IA2A and ZNT8 at baseline
BSCORE_IAA: IAA AAb presence at baseline
BSCORE_IAA_ZNT8: presence of IAA and ZNT8 at baseline
BSCORE_numberAA: number of autoantibodies presented at baseline
BSCORE_ZNT8: ZNT8 presence at baseline
SEX: subject's sex

Contact us

Juan Francisco Morales & Sarah Kim (E-mail: sarahkim@cop.ufl.edu)
This T1D Clinical Trial Simulator was developed based on the published disease progression model. Reference: Morales, JF, et al. Disease progression joint model predicts time to type 1 diabetes onset: Optimizing future type 1 diabetes prevention studies. CPT: Pharmacometrics & Systems Pharmacology. 2023; 12:1016–1028.

Acknowledgments & Disclosures

This work was funded by JDRF (grant numbers: 2-SRA-2020-903-A-N and 3-SRA-2022-1157-S-B). The content of this publication does not necessarily reflect the views or policies of JDRF. The data from the TEDDY (The Environmental Determinants of Diabetes in the Young) and TrialNet studies reported here were supplied by the National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository. This presentation does not necessarily reflect the opinions or views of the TEDDY Study Group, TrialNet, the NIH NIDDK, or the NIDDK Central Repository. The presenting authors have no relevant conflicts of interest to disclose.
We thank Simulations Plus for the free usage of Simulx, which runs the simulation in the app.